Alkynes in synthesis

Hosseini-Sarvari, M. and Etmad, S. 2008. Nanosized zinc oxide as a catalyst for the rapid and green synthesis of P-phosphono malonates. Tetrahedron 64 5519—5523. Hosseini-Sarvari, M. and Mardaneh, Z. 2011a. Selective and CO-ietentive addition reactions of acid chlorides to terminal alkynes in synthesis of P-chloro-a, P-unsaturated ketones using ZnO. Bull. Chem. Soc. Japan 84 ... 

Alkynylborate Salts and Hydroboration. The intense interest in the applications of trialkylalkynylborates (viz. 134) and of hydroboration of alkynes in synthesis has remained at a high level, and several papers have been published during the period covered by this Report, some of which are full descriptions of previously published communications. The synthetically useful transformations are shown diagrammatically in Table 14. 

Solved Exercise 13-19 Working with the Concepts Using Alkynes in Synthesis... 

CoF is used for the replacement of hydrogen with fluorine in halocarbons (5) for fluorination of xylylalkanes, used in vapor-phase soldering fluxes (6) formation of dibutyl decalins (7) fluorination of alkynes (8) synthesis of unsaturated or partially fluorinated compounds (9—11) and conversion of aromatic compounds to perfluorocycHc compounds (see Fluorine compounds, organic). CoF rarely causes polymerization of hydrocarbons. CoF is also used for the conversion of metal oxides to higher valency metal fluorides, eg, in the assay of uranium ore (12). It is also used in the manufacture of nitrogen fluoride, NF, from ammonia (13). 

The original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

Scheme 12 General synthesis of 5-dialkylamino-3-ethoxycyclopentadienes 60 from 3-di-alkylamino-l-ethoxypropenylidenechromium complexes 57 and alkynes in a donor solvent. Conditions A pyridine, 55-80 °C, 1.5-4 equiv. of the alkyne B MeCN, 80 °C, slow addition of 2-4 equiv. of the alkyne. For further details see Table 1 [43,44,60,61]...

The thermal benzannulation of Group 6 carbene complexes with alkynes (the Dotz reaction) is highly developed and has been used extensively in synthesis [90,91]. It is thought to proceed through a chromium vinylketene intermediate generated by sequential insertion of the alkyne followed by carbon monoxide into the chromium-carbene-carbon double bond [92]. The realization that photodriven CO insertion into Z-dienylcarbene complexes should generate the same vinylketene intermediate led to the development of a photochemical variant of the Dotz reaction (Table 14). 

At this point in time carboalumination of alkynes has been more widely applied in synthesis. The most frequently used catalyst is (Cp)2ZrCl2. It is believed that a bimetallic species is formed.227... 

Scheme 4.10 gives some examples of application of alkyne carboalumination in synthesis. The reaction in Entry 1 was carried out as part of a synthesis of the immunosuppressant drug FK-506. The vinyl alane was subsequently transmetallated to a cuprate reagent (see Chapter 8). In Entry 2, the vinyl alane was used as a nucleophile for opening an epoxide ring and extending the carbon chain by two atoms. In Entries 3 to 5, the vinyl alane adducts were converted to vinyl iodides. In Entry 6, the vinyl alane was converted to an ate reagent prior to reaction with formaldehyde. 

The coupling of terminal alkynes with organic halides, known as the Castro-Stephens-Sonogashira reaction, has wide applications in synthesis. The most widely used method is the Sonogashira coupling, using a combination of palladium and copper as the catalyst.13 Recently,... 

Arylation of alkynes via addition of arylboronic acids to alkynes represents an attractive strategy in organic synthesis. The first addition of arylboronic acids to alkynes in aqueous media catalyzed by rhodium was reported by Hayashi et al.89 They found that rhodium catalysts associated with chelating bisphosphine ligands, such as 1,4-Ws(diphenyl-phosphino)butane (dppb) and 1,1 -/ E(diphenylphospliino)fcrroccnc... 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

Stille JK (1991) Hydroformylation and related additions of carbon monoxide to alkenes and alkynes. In Trost BM, Fleming I, Paquette LA (eds) Comprehensive organic synthesis. Pergamon, Oxford, p 913... 

Kitching employed the titanium (Il)-based czs-reduction of alkynes in their synthesis of (3 ,8Z,llZ)-3,8,ll-tetradecatrienyl acetate (9), the pheromone of the moth Scrobipalpuloides absoluta as shown in Scheme 15 [15]. 

The utilization of solid-support pyridinium salts in the synthesis of bicyclic pyridines has been reported. Yue et al. synthesized 1,2,3,7-tetrasubstituted indolizines using poly(ethyleneglycol)bound pyridinium salts <06JHC781>. The PEG-bound pyridinium salts 53 were reacted with alkenes or alkynes in the presence of Et3N, via 1,3-dipolar cycloaddition, to give polymer-bound indolizines 54 and 55, respectively. Liberation of the heterocycle with KCN/MeOH afforded 1,2,3,7-tetrasubstituted indolizines 56 and 57 in good to excellent yield. 

Otera and coworkers developed an alternative procedure to the Julia method for generating dienes or alkynes in the same reaction by the double elimination of /J-acetoxy or /1-alkoxy sulphones with potassium /-butoxide (equation 58)98,99. The reaction pathway leading to the diene or an alkyne depends on the substrate structure and the reaction conditions. If an allylic hydrogen is present in the substrate then diene is formed, otherwise, the alkyne is the product of the reaction. This modified Julia methodology has een applied to the synthesis of vitamin A (equation 59)100, alkaloids piperine (equation and trichonine (equation 61)102. 

Stereodehned alkenyl cuprates add to alkynes in syn fashion to result in 1,3-dienes of predictable stereochemistry288. Naso and coworkers used this method for the synthesis... 

Various transition metal complexes, in particular of late transition metals, were reported to be effective catalysts for such double bond isomerization. Because organic synthesis is the focus of this volume, this section will cover the transition metal-catalyzed isomerization of alkenes, which has the significant synthetic and industrial utilities. This chapter will also include the synthetic application, asymmetric reactions,4-6 and isomerization of alkynes, in particular, that of propargylic alcohols. 

Addition of a boron-boron bond across a carbon-carbon triple bond is known for some 40 years since the finding that diboron tetrahalides add to alkenes and alkynes in the absence of catalysts.36 Although the reaction seemed to be potentially attractive, the instability of diboron tetrahalides was the critical drawback for the practical use in synthesis. In 1993, much more stable pinacol ester derivative of diboron was found to add to alkynes in the presence of platinum catalysts such as Pt(PPh3)4, Pt(CH2=CH2)(PPh3)2, and Pt(CO)2(PPh3)2 (Figure 1, Scheme 2).37,38 Other... 

In addition to transition metals, recent work has demonstrated that strong Lewis acids will catalyze the addition of silanes to alkynes in both an intra- and an intermolecular fashion.14,14a-14c The formation of vinylsilanes from alkynes is possible by other means as well, such as the synthetically important and useful silylcupration15,15a of alkynes followed by cuprate protonation to afford vinylsilanes. These reactions provide products which can be complementary in nature to direct hydrometallation. Alternatively, modern metathesis catalysts have made possible direct vinylsilane synthesis from terminal olefins.16,16a... 

Allenylcobaloximes, e.g. 26, react with bromotrichloromethane, carbon tetrachloride, trichloroacetonitrile, methyl trichloroacetate and bromoform to afford functionalized terminal alkynes in synthetically useful yields (Scheme 11.10). The nature of the products formed in this transformation points to a y-specific attack of polyhaloethyl radicals to the allenyl group, with either a concerted or a stepwise formation of coba-loxime(II) 27 and the substituted alkyne [62, 63]. Cobalt(II) radical 27 abstracts a bromine atom (from BrCCl3) or a chlorine atom (e.g. from C13CCN), which leads to a regeneration of the chain-carrying radical. It is worth mentioning that the reverse reaction, i.e. the addition of alkyl radicals to stannylmethyl-substituted alkynes, has been applied in the synthesis of, e.g., allenyl-substituted thymidine derivatives [64],... 

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